Various publications, including patents, published applications, technical articles and scholarly articles are cited throughout the specification. Each of these cited publications is incorporated by reference herein, in its entirety and for all purposes.
Traditional wound healing methods includes using topical liquid or semi-solid formulations. Such topical formulations typically only maintain contact with the wound for a short period of time, or may be rapidly absorbed, in either case limiting the efficiency of the formulation toward facilitating wound healing. Although dressings such as gauze, cotton, wool, and bandages can maintain the formulation in the vicinity of the wound for longer, the inability to maintain moisture may impede the effects of the dressings.
For more serious wounds, tissue adhesives, hydrocolloids, hydrogels, polymer films, biological dressings, foam dressings, and alginate may be used as a wound dressing. In addition, cyanoacrylate-based tissue adhesives may be used. Cyanoacrylate adhesives offer advantages over sutures or staples insofar as they produce lower infection rates.
It is believed that some cyanoacrylate compositions may have antimicrobial properties, although this has not translated into enhancing wound healing. Accordingly, some cyanoacrylate adhesive compositions for medical uses have wound healing accelerating agents incorporated therein. For example, U.S. Pat. Nos. 5,684,042, 5,762,919, 5,811,091, and 5,783,177 and U.S. Publication No. 20050042266 describe the inclusion of antimicrobial agents in a cyanoacrylate adhesive composition, for purposes of promoting wound healing.
Nevertheless, it is difficult to incorporate different additives into cyanoacrylate adhesives. First, most additives are not soluble in or miscible with cyanoacrylates. Second, of those additives that may dissolve, most affect the polymerization of the monomers—either by inhibiting it (renders the adhesive useless) or causing it (prevents shelf storage or disposition from a container). Thus, the cyanoacrylate could be prevented from curing (polymerizing) or induced to prematurely polymerize resulting in an undesirable reduction or destruction of the shelf-life stability of the cyanoacrylate. Third, some additives affect the viscosity of the composition. Fourth, some additive affect the performance of the composition in terms of elongating the cure time and diminishing the bonding strength. Fifth, some additives interact with the cyanoacrylate monomers, which in turn inactivates the additives or diminishes their efficacy as explained in U.S. Pat. No. 5,684,042. Sixth, cyanoacrylate adhesives are difficult to sterilize because all known sterilization modalities induce polymerization of the monomers, and additives tend to further facilitate this sterilization-induced polymerization. Thus, cyanoacrylate adhesives present many challenges of compatibility for potential wound healing accelerating agents.
Therefore a need remains for imparting wound-healing properties into cyanoacrylate adhesive compositions used for medical purposes via wound-healing additives that do not harm the integrity of the cyanoacrylate monomers or the additives themselves. A further need remains for the ability to sterilize wound-healing agent-containing cyanoacrylate adhesive compositions without affecting the shelf stability of the composition.